title: Overexpression of insulin-like growth factor-I receptor as a pertinent biomarker for hepatocytes malignant transformation.
abstract: OBJECTIVE
  To investigate the dynamic features of insulin-like growth factor-I receptor (IGF-IR) expression in rat hepatocarcinogenesis, and the relationship between IGF-IR and hepatocytes malignant transformation at mRNA or protein level.
  
  
  METHODS
  Hepatoma models were made by inducing with 2-fluorenylacetamide (2-FAA) on male Sprague-Dawley rats. Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining, the dynamic expressions of liver and serum IGF-IR were quantitatively analyzed by an enzyme-linked immunosorbent assay. The distribution of hepatic IGF-IR was located by immunohistochemistry. The fragments of IGF-IR gene were amplified by reverse transcription-polymerase chain reaction, and confirmed by sequencing.
  
  
  RESULTS
  Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration, precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-IR expression. The incidences of liver IGF-IR, IGF-IR mRNA, specific IGF-IR concentration (ng/mg wet liver), and serum IGF-IR level (ng/mL) were 0.0%, 0.0%, 0.63 ± 0.17, and 1.33 ± 0.47 in the control; 50.0%, 61.1%, 0.65 ± 0.2, and 1.51 ± 0.46 in the degeneration; 88.9%, 100%, 0.66 ± 0.14, and 1.92 ± 0.29 in the precancerosis; and 100%, 100%, 0.96 ± 0.09, and 2.43 ± 0.57 in the cancerous group, respectively. IGF-IR expression in the cancerous group was significantly higher (P < 0.01) than that in any of other groups at mRNA or protein level. The closely positive IGF-IR relationship was found between livers and sera (r = 0.91, t = 14.222, P < 0.01), respectively.
  
  
  CONCLUSIONS
  IGF-IR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation.
authors.affiliation: Xiao-Di Yan, Hai-Jian Zhang, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Yan
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Zhi-Zhen
authors.initials: ZZ
authors.lastname: Dong
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yao
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D015073:2-Acetylaminofluorene; D017526:Receptor, IGF Type 1
keywords: Gene amplification; Hepatoma; Immunohistochemistry; Insulin-like growth factor-I receptor; Rat hepatoma model; Sequencing